Mutations in PIEZO2 Cause Gordon Syndrome, Marden-Walker Syndrome, and Distal Arthrogryposis Type 5

被引：188

作者：

McMillin, Margaret J. ^{[1
]}

Beck, Anita E. ^{[1
,2
]}

Chong, Jessica X. ^{[1
]}

Shively, Kathryn M. ^{[1
]}

Buckingham, Kati J. ^{[1
]}

Gildersleeve, Heidi I. S. ^{[1
]}

Aracena, Mariana I. ^{[3
,4
]}

Aylsworth, Arthur S. ^{[5
,6
]}

Bitoun, Pierre ^{[7
]}

Carey, John C. ^{[8
]}

Clericuzio, Carol L. ^{[9
]}

Crow, Yanick J. ^{[10
,11
]}

Curry, Cynthia J. ^{[12
]}

Devriendt, Koenraad ^{[13
]}

Everman, David B. ^{[14
]}

Fryer, Alan ^{[15
]}

Gibson, Kate ^{[16
]}

Uzielli, Maria Luisa Giovannucci ^{[17
]}

Graham, John M., Jr. ^{[18
]}

Hall, Judith G. ^{[19
,20
,21
]}

Hecht, Jacqueline T. ^{[22
]}

Heidenreich, Randall A. ^{[9
]}

Hurst, Jane A. ^{[23
]}

Irani, Sarosh ^{[24
]}

Krapels, Ingrid P. C. ^{[25
]}

Leroy, Jules G. ^{[26
]}

Mowat, David ^{[27
,28
]}

Plant, Gordon T. ^{[29
]}

Robertson, Stephen P. ^{[30
]}

Schorry, Elizabeth K. ^{[31
]}

Scott, Richard H. ^{[23
]}

Seaver, Laurie H. ^{[32
]}

Sherr, Elliott ^{[33
]}

Splitt, Miranda ^{[34
]}

Stewart, Helen ^{[35
]}

Stumpel, Constance ^{[25
]}

Temel, Sehime G. ^{[36
,37
,38
]}

Weaver, David D. ^{[39
]}

Whiteford, Margo ^{[40
]}

Williams, Marc S. ^{[41
]}

Tabor, Holly K. ^{[2
,42
]}

Smith, Joshua D. ^{[43
]}

Shendure, Jay ^{[43
]}

Nickerson, Deborah A. ^{[43
]}

Washington, Univ

Bamshad, Michael J. ^{[1
,2
,43
]}

机构：

[1] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

[2] Seattle Childrens Hosp, Div Med Genet, Seattle, WA 98105 USA

[3] Hosp Dr Luis Calvo Mackenna, Genet Unit, Santiago 7500539, Chile

[4] Pontificia Univ Catolica Chile, Div Pediat, Santiago 8330074, Chile

[5] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[7] Hop Jean Verdier, AP HP, Serv Pediat, F-93143 Bondy, France

[8] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA

[9] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA

[10] Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, England

[11] Univ Manchester, Manchester M13 9NT, Lancs, England

[12] Univ Calif San Francisco, Fresno, CA 93701 USA

[13] Univ Hosp KU Leuven, Ctr Human Genet, B-3000 Louvain, Belgium

[14] Greenwood Genet Ctr, Greenwood, SC 29646 USA

[15] Alder Hey Childrens Hosp, Dept Clin Genet, Liverpool L12 2AP, Merseyside, England

[16] Christchurch Hosp, Genet Hlth Serv New Zealand, Christchurch 8140, New Zealand

[17] Univ Florence, Dipartimento Sci Salute, I-50132 Florence, Italy

[18] Cedars Sinai Med Ctr, Div Clin Genet & Dysmorphol, Los Angeles, CA 90048 USA

[19] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada

[20] Univ British Columbia, Dept Pediat, Vancouver, BC V6H 3N1, Canada

[21] BC Childrens Hosp, Vancouver, BC V6H 3N1, Canada

[22] Univ Texas Med Sch, Dept Pediat, Houston, TX 77030 USA

[23] Great Ormond St Hosp Sick Children, North East Thames Reg Genet Serv, London WC1N 3BH, England

[24] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England

[25] Maastricht UMC, Dept Clin Genet, Sch Oncol & Dev Biol, NL-6229 GR Maastricht, Netherlands

[26] Ghent Univ Hosp, Princess Elisabeth Childrens Hosp, B-9000 Ghent, Belgium

[27] Sydney Childrens Hosp, Dept Med Genet, Sydney, NSW 2031, Australia

[28] Univ New S Wales, UNSW Med, Sch Womens & Childrens Hlth, Sydney, NSW 2052, Australia

[29] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England

[30] Univ Otago, Dept Womens & Childrens Hlth, Dunedin 9054, New Zealand

[31] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA

[32] Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96826 USA

[33] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[34] Inst Med Genet, Northern Genet Serv, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[35] Oxford Univ Hosp NHS Trust, Churchill Hosp, Dept Clin Genet, Oxford 0X3 7LJ, England

[36] Uludag Univ, Fac Med, Dept Med Genet, TR-16059 Bursa, Turkey

[37] Uludag Univ, Fac Med, Dept Histol & Embryol, TR-16059 Bursa, Turkey

[38] Near East Univ, Fac Med, Dept Histol & Embryol, TR-10 Trnc Mersin, Turkey

[39] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[40] So Gen Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, Scotland

[41] Geisinger Hlth Syst, Genom Med Inst, Danville, PA 17822 USA

[42] Seattle Childrens Res Inst, Treuman Katz Ctr Pediat Bioeth, Seattle, WA 98101 USA

[43] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2014年 / 94卷 / 05期

关键词：

CLEFT-PALATE; SPECTRUM; DELINEATION; CONGENITA; FAMILY; IIB;

D O I：

10.1016/j.ajhg.2014.03.015

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Gordon syndrome (GS), or distal arthrogyposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechano-sensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.

引用

页码：734 / 744

页数：11

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